2016 Fiscal Year Annual Research Report
Ｂリンパ球の分化と自己免疫に関するマウスｇｐ４９Ｂの機能解析
| Project/Area Number |
16J01922
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| Research Institution | Tohoku University |
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Principal Investigator |
WONG YI LI 東北大学, 生命科学研究科, 特別研究員(DC1)
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| Project Period (FY) |
2016-04-22 – 2019-03-31
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| Keywords | gp49B / autoimmunity |
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| Outline of Annual Research Achievements |
To determine the association of the residual expression of gp49B with transcription of plasma cells from BXSB mice, plasmablasts were generated by in vitro stimulations and analyzed for the surface expression of gp49B. Stimulation of B lymphocytes (naive B cells and marginal zone B cells) with TLR ligands such as LPS and R848, and cytokines such as IL-4, IL-6 and IL-10, had minimal effect on inducing high level of surface expression of gp49B on the plasmablasts generated. Inclusion of pathogenic stimuli related to SLE disease activity such as IL-2 and IFN-α was hypothesized to induce surface gp49B on the plasmablasts generated. However, the expression level of gp49B was not as high as expected or not comparable to primary splenic plasma cells.
The initial study of gp49B deficiency in autoimmune-prone mice was performed on FcγRIIB deficient-SLAM129 mice (RIIB-/-SLAM129). Initial observation of the phenotypes of gp49B knockout RIIB-/-SLAM129 mice was ameliorated the disease partially, with reduced splenomegaly and serum level anti-DNA autoantibodies.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
There is a delay in the establishment of gp49B-knockout BXSB model, where the backcross of gp49B deficient C57BL/6 mice to BXSB/Yaa mice is up to the 7th generation currently.
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| Strategy for Future Research Activity |
To overcome the delay in backcrossing gp49B-knockout C57BL/6 mice into BXSB mice background, current study of the role of gp49B in mouse model with SLE-like manifestations is performed on FcγRIIB deficient-SLAM129 mice. This double knockout model will be analyzed further on the function of gp49B on pathogenic plasma cell formation in vitro. The effect of gp49B interaction with its potential ligands will be studied (by in vitro culture system), particularly on the survival of pathogenic plasma cells and autoantibodies production.
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